Delineação Clínica e Molecular da Síndrome de Joubert Associada ao Gene AHI1 numa Linhagem Consanguínea: Caso Clínico

Autores

  • Doaa Haqi Ismael Cancer Researches Department, Iraqi Center for Cancer and Medical Genetic Research, Mustansiriyah University, Baghdad, Iraq
  • Almuthana K. Hameed Department of Medical Physics, College of Applied Sciences-Heet, University of Anbar, Iraq https://orcid.org/0009-0005-4949-1810
  • Shaymaa Muneam Saeed Department of Biology, University of Misan, Misan, Iraq
  • Sahar Kareem Al-Mozani Department of Biology, University of Misan, Misan, Iraq https://orcid.org/0009-0001-2439-7124
  • Kamele Jorfi Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran https://orcid.org/0009-0009-3293-053X
  • Motahareh Sheikh-Hosseini Pediatric Cell & Gene Therapy Research Center, Tehran University of Medical Sciences, Tehran, Iran https://orcid.org/0000-0001-5746-5376
  • Ehab Neissi Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

DOI:

https://doi.org/10.46531/sinapse/CC/169/2025

Palavras-chave:

Anomalias Congénitas Múltiplas/genética, Ciliopatias/genética, Criança, Encefalopatias/ diagnóstico, Encefalopatias/genética, Proteínas Adaptadoras de Transdução de Sinal/genética, Sequenciação do Exoma, Sindrome de Joubert/ diagnóstico

Resumo

Contexto: A síndrome de Joubert (SJ) é uma doença neurodesenvolvimental rara, autossómica recessiva, caracterizada pelo sinal do "dente molar" (SDM) na ressonância magnética cerebral, resultante da hipoplasia do vérmis cerebelar e dos pedúnculos cerebelares superiores alongados.

Métodos: Uma criança do sexo feminino, de 4 anos, apresentando atraso global do desenvolvimento, hipotonia, apraxia oculomotora e SDM na ressonância magnética, foi submetida a sequenciação do exoma completo (SEC). Foram realizadas análises bioinformáticas, validação por Sanger e estudos de segregação. A patogenicidade foi avaliada segundo as diretrizes ACMG/AMP e ferramentas in silico.

Resultados: A SEC revelou uma variante homozigótica nonsense nova no gene AHI1 (c.2938A>T; p.Lys980Ter), ausente em bases de dados populacionais. A análise de segregação confirmou herança autossómica recessiva, com ambos os pais como portadores heterozigotos. A conservação evolutiva da Lis980 reforçou a sua importância funcional.

Conclusão: Este estudo amplia o espectro mutacional da SJ associada ao AHI1 e destaca a utilidade da SEC em populações consanguíneas. Os achados facilitam o diagnóstico preciso, o aconselhamento genético e o planeamento reprodutivo informado para famílias em risco.

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Publicado

2025-10-29

Como Citar

1.
Haqi Ismael D, K. Hameed A, Muneam Saeed S, Kareem Al-Mozani S, Jorfi K, Sheikh-Hosseini M, et al. Delineação Clínica e Molecular da Síndrome de Joubert Associada ao Gene AHI1 numa Linhagem Consanguínea: Caso Clínico. Sinapse [Internet]. 29 de Outubro de 2025 [citado 2 de Novembro de 2025];. Disponível em: https://sinapse.pt/index.php/journal/article/view/169

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Direitos de Autor (c) 2024 Doaa Haqi Ismael, Almuthana K. Hameed, Shaymaa Muneam Saeed, Sahar Kareem Al-Mozani, Kamele Jorfi, Motahareh Sheikh-Hosseini, Ehab Neissi

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Este trabalho encontra-se publicado com a Creative Commons Atribuição-NãoComercial 4.0.